Scientists Find Brain Cholesterol Link to Alzheimer's-Like Damage

Ask your doctor how to prevent this problem noting these two items:

1. Although cholesterol cannot cross the BBB, some cholesterols are absorbed into the brain in the form of plasma lipoprotein-bound cholesterol [40, 41].

2. Brain cholesterol is synthesized in situ by astrocytes and oligodendrocytes and is almost completely isolated from other pools of cholesterol in the body, but a small fraction can be taken up from the circulation as 27-hydroxycholesterol, or via the scavenger receptor class B type I. 

Scientists Find Brain Cholesterol Link to Alzheimer's-Like Damage

Cholesterol could possibly be linked to increased risks of cognitive decline and dementia.Deposits of proteins known as tau—associated with the onset of Alzheimer's disease—in the brain are connected to the accumulation of a form of cholesterol known as cholesteryl esters, according to new research in the journal Neuron.Tangles of tau proteins in the brain drive cognitive decline, as it causes nearby brain tissue to start to degenerate. In the United States, about 5.8 million adults have Alzheimer's disease and other dementias, according to the U.S. Centers for Disease Control and Prevention."This has important therapeutic implications," paper co-author David M. Holtzman, a professor of neurology at the Washington University School of Medicine in St. Louis, said in a statement.One genetic risk factor for Alzheimer's disease is a gene called APOE, which activates immune cells in the brain that can cause damage to brain tissue if activated in the wrong way or at the wrong time. APOE is also involved in the The researchers tested the connection between the APOE gene, cholesterol, and brain damage by modifying the gene in mice. These mice already had a high-risk tau gene that makes them accumulate tau rapidly, showing neurodegeneration at six months of age and having severe brain damage by 9.5 months to the point where they can no longer perform basic tasks.Related video: Study: Bigger Bellies Linked to Alzheimer's Risk (Dailymotion)Some of the mice had their APOE genes removed and replaced with human APOE genes—some with APO3, which has an average risk of Alzheimer's, and APOE4, which doubles or even triples the risk. Other mice did not have the gene replaced at all.The researchers found that mice that carried APOE4 had distorted brain lipid metabolism, meaning that the same areas of their brain that were damaged by tau were accumulating strange patterns of lipids, including cholesterol and over 180 other types. Immune microglia cells were found to be filled with cholesteryl esters. "Microglia filled up with lipids become hyperinflammatory and start secreting things that are not good for the brain," Holtzman said.APO3 did not cause this effect on the brain, the researchers found. To determine if removing the lipids could prevent neurodegeneration in the mice, the researchers used an experimental drug known as an LXR agonist which lowers cell lipid levels. When the APOE4 mice were given the drug, named GW3965, the scientists found that those whose brains would usually show large amounts of damage had a lot more brain volume than the mice who took the placebo drug.